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Richard Sullivan

Publications and source records attributed to Richard Sullivan.

15 recordsLinked to original sources
PubMed2006

Use of quantum dot luminescent probes to achieve single-cell resolution of human oral bacteria in biofilms.

Oral biofilms are multispecies communities, and in their nascent stages of development, numerous bacterial species engage in interspecies interactions. Better insight into the spatial relationship between different species and how species diversity increases over time can guide our understanding of the role of interspecies interactions in the development of the biofilms. Quantum dots (QD) are semiconductor nanocrystals and have emerged as a promising tool for labeling and detection of bacteria. We sought to apply QD-based primary immunofluorescence for labeling of bacterial cells with in vitro and in vivo biofilms and to compare this approach with the fluorophore-based primary immunofluorescence approach we have used previously. To investigate QD-based primary immunofluorescence as the means to detect distinct targets with single-cell resolution, we conjugated polyclonal and monoclonal antibodies to the QD surface. We also conducted simultaneous QD conjugate-based and fluorophore conjugate-based immunofluorescence and showed that these conjugates were complementary tools in immunofluorescence applications. Planktonic and biofilm cells were labeled effectively by considering two factors: the final nanomolar concentration of QD conjugate and the amount of antibody conjugated to the QD, which we define as the degree of labeling. These advances in the application of QD-based immunofluorescence for the study of biofilms in vitro and in vivo will help to define bacterial community architecture and to facilitate investigations of interactions between bacterial species in these communities.

Antibodies, Monoclonal↗
PubMed2006

Adjuvant chemotherapy for non-small cell lung cancer: a New Zealand perspective.

This article reviews recent developments with the use of adjuvant chemotherapy for resected early-stage non-small cell lung cancer (NSCLC) and the implications of these developments for healthcare in New Zealand (NZ). Non-small cell lung cancer is a major cause of mortality and morbidity in NZ, and is greatly over-represented among Maori and socioeconomically deprived populations. Early-stage NSCLC is potentially curable by surgery, but long-term outcome after surgical resection is limited by disease recurrence locally or at sites distant from the primary disease. Three recent large randomised controlled phase III trials using modern platinum-based combination chemotherapy protocols have shown significant survival benefits for the use of postoperative adjuvant chemotherapy after resection of early-stage NSCLC. Cisplatin plus vinorelbine was used as the adjuvant chemotherapy regimen in two of these trials resulting in improvements in 5-year survival of 51.2% versus 42.6% (p=0.013) and 69% versus 54% (p=0.03), respectively. In NZ, adjuvant chemotherapy for NSCLC is expected to prevent up to 15 lung cancer deaths each year for relatively low drug expenditure and has the potential to benefit Maori and the economically-deprived disproportionately more than other populations. In conclusion, it is the opinion of this group of NZ lung cancer specialists that adjuvant chemotherapy with cisplatin plus vinorelbine should now be adopted as a standard of care for patients with resected stage II and III NSCLC. For this to occur, current PHARMAC policies preventing its use for these eligible patients will need to be revised.

Antineoplastic Agents, Phytogenic↗
PubMed2006

Medicinal mushrooms and cancer therapy: translating a traditional practice into Western medicine.

Modern medical practice relies heavily on the use of highly purified pharmaceutical compounds whose purity can be easily assessed and whose pharmaceutical activity and toxicity show clear structure-function relationships. In contrast, many herbal medicines contain mixtures of natural compounds that have not undergone detailed chemical analyses and whose mechanism of action is not known. Traditional folk medicine and ethno-pharmacology coupled to bioprospecting have been an important source of many anticancer agents as well as other medicines. With the current decline in the number of new molecular entities from the pharmaceutical industry, novel anticancer agents are being sought from traditional medicine. As the example of medicinal mushrooms demonstrates, however, translating traditional Eastern practices into acceptable evidence-based Western therapies is difficult. Different manufacturing standards, criteria of purity, and under-powered clinical trials make assessment of efficacy and toxicity by Western standards of clinical evidence difficult. Purified bioactive compounds derived from medicinal mushrooms are a potentially important new source of anticancer agents; their assimilation into Western drug discovery programs and clinical trials also provides a framework for the study and use of other traditional medicines.

Agaricales↗
PubMed2005

Nitric oxide signalling and cellular adaptations to changes in oxygenation.

Fluctuations in oxygen (O2) levels characterise the cellular microenvironment in physiological and pathological processes such as placentation and malignant progression. Cells adapt to such changes in oxygenation by modifying gene expression, thereby regulating a spectrum of functions. Recent studies indicate that an important mechanism by which cells adapt to changes in oxygenation involves modifications in endogenous nitric oxide (NO) signalling. The effect of oxygen on the NO pathway involving cyclic guanosine monophosphate (cGMP)-dependent signalling appears to play a critical role in the regulation of cellular phenotypes. This specific NO signalling pathway may also operate in conjunction with gene expression regulated by the transcription molecule hypoxia inducible factor 1 (HIF-1). Thus, NO is emerging as a novel regulator of oxygen-sensitive phenotypes.

Animals↗
PubMed2005

In situ and non-invasive detection of specific bacterial species in oral biofilms using fluorescently labeled monoclonal antibodies.

Noninvasive in situ detection of suspected cariogenic bacterial species within dental biofilms could facilitate monitoring of the dynamic change of oral microbial flora and assist in the assessment of the treatment efficacy of therapeutic agents. In this study, we explore the possibility to use three well-characterized monoclonal antibodies (MAbs) against Streptococcus mutans, Actinomyces naeslundii, and Lactobacillus casei to identify these three important members of the oral microbial community in the complex environment of oral biofilms. These MAbs, which were conjugated to different fluorescent labels and visualized with confocal laser scanning microscopy (CLSM), proved to be an useful tool to identify the three species of interest (S. mutans, A. naeslundii, and L. casei) under various experimental conditions including in vitro and in vivo derived oral biofilms. Manifold addition of the MAbs on consecutive days did not alter the biofilm structure thus allowing monitoring of the same biofilm over extended time periods. Using this MAb-based method the effect of sucrose challenge on the biofilm composition and the distribution of S. mutans, A. naeslundii, and L. casei were examined. S. mutans was found to be the predominant species under the various biofilm conditions tested. These studies indicate that MAbs based bacterial detection with CLSM is a versatile tool which permits new insights into the ecology of oral biofilm development.

Actinomyces↗
PubMed2004

Non-disruptive, real-time analyses of the metabolic status and viability of Streptococcus mutans cells in response to antimicrobial treatments.

Streptococcus mutans is one of a small number of recognized pathogens that lives among the hundreds of other bacterial species which comprise the oral flora. The virulence of this organism is intimately associated with its ability to live as an attached biofilm community on the tooth surface, and consequently, there is a great interest in its biofilm lifestyle. Currently, there are no established protocols that facilitate drug screening against this organism while it is entrenched in the biofilm. Furthermore, greater complications arise when attempting to perform these experiments in a multi-species setting. In an effort to circumvent these problems, we developed a quick, real-time, and non-disruptive method to probe the metabolic status of S. mutans growing as either a planktonic culture or a biofilm community. This assay takes advantage of the proven utility of luciferase measurements for drug screening. We placed the luciferase gene under the control of the S. mutans lactate dehydrogenase promoter (ldh) and integrated the construct onto its native position on the chromosome. We found this construct to be both highly expressed (<10000 cells easily detectable) and insensitive to many different growth parameters. When testing this reporter in both planktonic and biofilm cultures receiving either bacteriostatic or bactericidal antibiotics, we found the ldh-luc reporter to be a very accurate measurement of cell viability. Furthermore, we also demonstrated that this assay can generate useful information about the characteristics of intoxication caused by antibiotic activity. In addition, we modified the biofilm assay into the 96-well format and demonstrated the feasibility of high throughput drug screening of biofilm embedded S. mutans.

Anti-Bacterial Agents↗
PubMed2003

Evolutionary adaptation of a mammalian species to an environment severely depleted of iodide.

Lack of dietary iodine is associated with thyroid insufficiency and its dire consequences including cretinism, yet territories severely deficient in iodine are home to many species of wild animals. The premise of our work is that an adaptation must be in place in order to allow these animals to thrive. We collected phyllotine rodents of the genus Auliscomys from the Altiplanic region of North Chile, an area historically associated with goitre and other manifestations of iodine deficiency disorders. The iodide concentration in the stream water in this locality, at <1 micro g l(-1) would undoubtedly result in widespread thyroidal insufficiency in humans and domestic livestock. The animals we collected, identified as Auliscomys boliviensis, showed no evidence of thyroidal insufficiency. There was no enlargement of the thyroid glands; the serum concentrations of thyroid hormone (measured as T4) and thyroid-stimulating hormone were comparable to laboratory rats. Serum iodide concentration was about 40% of that measured in laboratory rats. We conclude that these animals have established a specialised adaptive mechanism, most probably at the level of the Na(+)/I(-) symporter, that acts to enhance the uptake of dietary iodide into the gut and again from the serum into the follicular cells of the thyroid gland.

Adaptation, Physiological↗
PubMed2002

Safety profile of a new liquid whitening gel.

Colgate Simply White Clear Whitening Gel, an at-home tooth-whitening product purchased over the counter, contains 18% carbamide peroxide (equivalent to 6.5% hydrogen peroxide) as the active ingredient in a brush-applied liquid gel. The excipients include ingredients commonly used in dentifrices. The potential for effects on the tooth pulp, oral soft tissue irritation, enamel damage, and tooth sensitivity with this peroxide-containing product have been evaluated. An in vitro study demonstrated that pulpal chamber hydrogen peroxide levels are well below those considered to cause an effect on pulpal tissue. An exaggerated-use (4 applications per day for 3 weeks) clinical study showed that no oral irritation occurred during 3 weeks of use. A study measuring peroxide salivary concentration after use of Colgate Simply White Clear Whitening Gel showed that the concentration of peroxide in the saliva after use of the product was extremely low, further supporting the position that this product has a low potential for causing oral irritation. Additional studies demonstrate that Colgate Simply White Clear Whitening Gel does not harm the enamel surface or produce demineralization after exposure equivalent to 3 weeks of normal use and over 6 weeks of exaggerated use. Colgate Simply White Clear Whitening Gel has not produced oral irritation (hard and soft tissues) or tooth hypersensitivity in a clinical subject population of 141 individuals using varying treatment regimens. These studies prove that Colgate Simply White Clear Whitening Gel is safe for daily use as directed.

Bicuspid↗
PubMedDate not supplied

Mediated reunions in adoption: findings from an evaluation study.

In Canada, there are long waiting lists of adopted persons and birthparents seeking information or actual reunions. In the province of Quebec, the government authorized a pilot project, involving a fee-for-service program and use of contract social workers to supplement agency staff as intermediaries in the reunion process. This article reports on the project's evaluation and provides birth-parents' and adoptees' responses to reunion. A survey of clients who used this service found a high level of satisfaction. There were, however, some significant differences between birthparents and adoptees as well as between those who were searching and those found.

Adoption↗